#USA, #Flu #Antiviral Drugs #Resistance: Two A #H1N1pdm09 viruses had NA-H275Y amino acid substitution conferring highly reduced #inhibition by #oseltamivir and #peramivir. One A #H1N1pdm09 virus had NA-I223V and NA-S247N amino acid substitutions and showed reduced inhibition by #oseltamivir. FluView: https://www.cdc.gov/fluview/surveillance/2025-week-05.html
Weekly US Influenza Surveillance Report: Key Updates for Week 5, ending February 1, 2025

Key Updates for Week 5, ending February 1, 2025

FluView

Source: Emerging Infectious Diseases Journal, https://wwwnc.cdc.gov/eid/article/30/11/24-0892_article

Abstract
Since 2013, a total of 167 human infections with swine-origin (variant) influenza A viruses of A(H1N1)v, A(H1N2)v, and A(H3N2)v subtypes have been reported in the United States. Analysis of 147 genome sequences revealed that nearly all had S31N substitution, an M2 channel blocker-resistance marker, whereas neuraminidase inhibitor–resistance markers were not found. Two viruses had a polymerase acidic substitution (I38M or E199G) associated with decreased susceptibility to baloxavir, an inhibitor of viral cap-dependent endonuclease (CEN). Using phenotypic assays, we established subtype-specific susceptibility baselines for neuraminidase and CEN inhibitors. When compared with either baseline or CEN-sequence–matched controls, only the I38M substitution decreased baloxavir susceptibility, by 27-fold. Human monoclonal antibodies FI6v3 and CR9114 targeting the hemagglutinin’s stem showed variable (0.03 to >10 µg/mL) neutralizing activity toward variant viruses, even within the same clade. Methodology and interpretation of laboratory data described in this study provide information for risk assessment and decision-making on therapeutic control measures.

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https://etidioh.wordpress.com/2024/10/09/antiviral-susceptibility-of-swine-origin-influenza-a-viruses-isolated-from-humans-usa/

#abstract #antivirals #baloxavir #drugsResistance #h1n1v #h1n2v #h3n2v #influenzaA #oseltamivir #peramivir #research

Antiviral Susceptibility of Swine-Origin Influenza A Viruses Isolated from Humans, United States

Antiviral Susceptibility of Swine-Origin Influenza

Emerging Infectious Diseases journal

Whole-Genome #Analysis of #Influenza #H1N1pdm09 Viruses Isolated from ILI #Outpatients in #Myanmar & CA #Oseltamivir-Resistant Strains Present from 2015 to 2019 https://pubmed.ncbi.nlm.nih.gov/39205274/?utm_source=Feedly&utm_medium=rss&utm_campaign=None&utm_content=10ykRO9og5pGdo51l9DEPEpOJ3DVFIn__QK2QPM3dci1C1dEYq&fc=None&ff=20240831103754&v=2.18.0.post9+e462414

3 viruses possessed the #H275Y substitution in #neuraminidase protein, appearing to be community-acquired without prior administration of neuraminidase inhibitors. These viruses exhibited highly reduced susceptibility to #oseltamivir and #peramivir.

Whole-Genome Analysis of the Influenza A(H1N1)pdm09 Viruses Isolated from Influenza-like Illness Outpatients in Myanmar and Community-Acquired Oseltamivir-Resistant Strains Present from 2015 to 2019 - PubMed

In this study, we describe the genetic characteristics of influenza A(H1N1)pdm09 strains detected in Myanmar from 2015 to 2019. Whole genomes from 60 A(H1N1)pdm09 virus isolates were amplified using real-time polymerase chain reaction and successfully sequenced using the Illumina iSeq100 platforms. …

PubMed

[Articles] #Antivirals for #treatment of severe #influenza: a systematic #review and network meta-analysis of randomised controlled trials https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01307-2/fulltext?rss=yes

In hospitalised patients with severe flu, #oseltamivir & #peramivir might reduce duration of hospitalisation compared with standard care or placebo, although certainty of evidence is low. Effects of all antivirals on mortality & other important patient outcomes are very uncertain due to scarce data from #RCTs.

Whole- #Genome #Analysis of #Influenza #H1N1pdm09 Viruses Isolated from #ILI #Outpatients in #Myanmar & Community-Acquired #Oseltamivir - #Resistant Strains Present from 2015 to 2019 https://www.mdpi.com/1999-4915/16/8/1300

1 virus intra-subtype reassortment, collected in the '15 season. 3 viruses possessed #H275Y substitution in NA protein, appearing to be CA without prior administration of neuraminidase #inhibitors. These viruses exhibited highly reduced susceptibility to #oseltamivir & #peramivir.

Whole-Genome Analysis of the Influenza A(H1N1)pdm09 Viruses Isolated from Influenza-like Illness Outpatients in Myanmar and Community-Acquired Oseltamivir-Resistant Strains Present from 2015 to 2019

In this study, we describe the genetic characteristics of influenza A(H1N1)pdm09 strains detected in Myanmar from 2015 to 2019. Whole genomes from 60 A(H1N1)pdm09 virus isolates were amplified using real-time polymerase chain reaction and successfully sequenced using the Illumina iSeq100 platforms. Eight individual phylogenetic trees were retrieved for each segment along with those of the World Health Organization (WHO)-recommended Southern Hemisphere vaccine strains for the respective years. A(H1N1)pdm09 viruses from 2015 were found to belong to clade 6B, those from 2016 to 6B.1, 2017 to 6B.1A, and 2019 to 6B.1A.5a, and were genetically distinct from the Southern Hemisphere vaccine strains for the respective seasons, A/California/7/2009 and A/Michigan/45/2015. We observed one virus with intra-subtype reassortment, collected in the 2015 season. Importantly, three viruses possessed the H275Y substitution in the neuraminidase protein, appearing to be community-acquired without the prior administration of neuraminidase inhibitors. These viruses exhibited highly reduced susceptibility to oseltamivir and peramivir. This study demonstrates the importance of monitoring genetic variations in influenza viruses that will contribute to the selection of global influenza vaccines.

MDPI

#h5n1 #birdflu #avianflu #hpai #h5n2 #influence #grippe #flu #press #news

#antivirale #Medikamente #Virostatika geg #Influenza:

#Oseltamivirphosphat (als Generikum od. unter Handelsnamen #Tamiflu)
#Zanamivir ( #Relenza )
#Peramivir ( #Rapivab )
#Baloxavir ( #Xofluza )
Bei bestätigter od. Verdacht auf #Vogelgrippe wird schnellstmögl. Behandlung empfohlen

Tiermodelle & #Beobachtungsstudien deuten auf Nutzen von Virostatika bei mit Vogelgrippe infizierten #Menschen hin

https://www.medscape.com/viewarticle/new-human-cases-avian-flu-anticipated-2024a1000bfg?form=fpf

New Human Cases of Avian Flu Anticipated

The symptoms can be classic respiratory problems, conjunctivitis, or less obvious gastrointestinal issues and the CDC says laboratories are ready to help with testing.

Medscape

#Antivirals for #treatment of severe #influenza: a systematic #review and network meta-analysis of randomized controlled trials, MedRxIV, https://www.medrxiv.org/content/10.1101/2024.05.28.24307938v1

In hospitalized patients with severe influenza, #oseltamivir and #peramivir may reduce duration of hospitalization compared with standard care or placebo. The effects of all antivirals on #mortality and other important patient outcomes are very uncertain.

Antivirals for treatment of severe influenza: a systematic review and network meta-analysis of randomized controlled trials

Background: The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza. Methods: We systematically searched Medline, Embase, CENTRAL, CINAHL, Global Health, Epistemonikos, and ClinicalTrials.gov for randomized controlled trials published through 20 September 2023, that enrolled hospitalized patients with suspected or laboratory-confirmed influenza and compared direct-acting influenza antivirals against placebo, standard care, or another antiviral. We conducted frequentist network meta-analyses to summarize the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We registered the protocol with PROSPERO, CRD42023456650. Findings: Of 11,878 records, 8 trials with 1,424 participants were included. The effects of oseltamivir, peramivir or zanamivir on mortality compared with placebo or standard care without placebo for seasonal and zoonotic influenza are uncertain. Compared with placebo or standard care, oseltamivir (mean difference (MD) 1.63 days lower, 95% CI 2.81 lower to 0.45 lower) and peramivir (MD 1.73 days lower, 95% CI 3.33 lower to 0.13 lower) may reduce duration of hospitalization for seasonal influenza (low certainty evidence). There were few or no differences between oseltamivir (MD 0.34 days higher, 95% CI 0.86 lower to 1.54 higher; low certainty evidence), peramivir (MD 0.05 days lower, 95% CI 0.69 lower to 0.59 higher; low certainty evidence) and standard care in time to alleviation of symptoms. There were no differences in adverse events or serious adverse events among oseltamivir, peramivir and zanamivir (very low certainty evidence). Interpretation: In hospitalized patients with severe influenza, oseltamivir and peramivir may reduce duration of hospitalization compared with standard care or placebo. The effects of all antivirals on mortality and other important patient outcomes are very uncertain. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols <https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=456650> ### Funding Statement This study was funded by WHO ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript

medRxiv
''Phenotypic testing of 22 clade 2.3.2.1a and 2.3.4.4b viruses revealed broad susceptibility to NAIs and #baloxavir concluding that most contemporary HPAI A(#H5N1) viruses retain susceptibility to #antiviral drugs. Novel NA-K432E and NA-T438I #substitutions (N2 numbering) were identified at **elevated frequencies** (104/2698, 3.85%) and caused reduced #zanamivir and #peramivir inhibition.''